title: Design and evaluation of baicalin-containing in situ pH-triggered gelling system for sustained ophthalmic drug delivery.
abstract: Baicalin has been reported to have anti-inflammatory and anti-cataract effects on eye tissues, but it has a low bioavailability partly due to its poor stability of baicalin, the special anatomic structure and efficient protective mechanism of eyes. The aim of this study was to investigate the correlation between the stability of baicalin and in situ pH-triggered gelling system. Carbopol(®) 974P (0.3%, w/v) was used as the gelling agent combined with hydroxypropylmethylcellulose E4M (0.6%, w/v) which acted as a viscosity enhancing agent. In vitro and in vivo evaluations were performed using several techniques, namely confocal scanning light microscopy analysis, rheometry, Gamma scintigraphic technique and microdialysis method. The rheological behavior showed a significant enhancement in gel strength under physiological conditions, and the formulation provided sustained release of the drug over an 8-h period. In elimination studies, the radioactivity of formulation was always higher than that of the control solution. Additionally, the AUC and C(max) values were 6.1-fold and 3.6-fold higher than those of the control solution, respectively. The results demonstrated that an in situ pH-triggered gelling system have better ability to keep baicalin stable and retain drug release than marketed baicalin eye drops to enhance the ocular bioavailability.
authors.affiliation: Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, 88 Yuquan Road, Tianjin 300193, PR China. whycloudy@163.com
authors.forename: Haoyun
authors.initials: H
authors.lastname: Wu
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.forename: Junjie
authors.initials: J
authors.lastname: Peng
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Jiawei
authors.initials: J
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005419:Flavonoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005782:Gels; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D018613:Microscopy, Confocal; D011817:Rabbits; D012212:Rheology; D014783:Viscosity
chemical_list: D000179:Acrylates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D005419:Flavonoids; D005782:Gels; C117167:carbopol 974P NF; C038044:baicalin; D065347:Hypromellose Derivatives; D008747:Methylcellulose